Dialkyl-1,2-dihydroquinoline and 1,2-dihydroisoquinoline phosphonates

ABSTRACT

NITROGEN-HETEROCYCLIC PHOSPHONATES WHEREIN THE PHOSPHONATE GROUP IS ORTHO- OR PARA- TO THE NITROGEN HETEROCYCLIC GROUP, WHERE THE COMPOUNDS ARE CHARACTERIZED AS FOLLOWS:   -O-P(=O)(-O-)-C&lt;(--N-) ORTHO SUBSTITUTED AND   -O-P(=O)(-O-)-C&lt;(--N-C-C-) PARA SUBSTITUTED   WHEREIN THE DOTTED LINE REPRESENTS A CYCLIC STRUCTURE WHICH CYCLIC STRUCTURE MAY BE THE SOLE CYCLIC STRUCTURE, OR MAY BE ATTACHED TO OTHER CYCLIC GROUPS. THESE NITROGEN HETEROCYCLIC PHOSPHONAATES ARE PREPARED BY REACTING AN AROMATIC NITROGEN HETEROCYCLIC COMPOUND WHEREIN THE NITROGEN ATOM IS IN THE FORM OF A SALT OR A QUATERNARY, WITH A PHOSPHITE SALT, PREFERABLY IN THE FORM OF ESTERS OF THE PHOSPHITE AS EXEMPLIFIED BY THE FOLLOWING EQUATION:   R&#39;&#39;-N(+)&lt;(=C-C=C--) + M-P(=O)(-O-R)2 --&gt; O=P(-O-R)2(-C&lt;(-   C-C--C(-R&#39;&#39;)-)) AND/OR O=P(-O-R)2(-C&lt;(-C=C-N(-R&#39;&#39;)-))   THESE COMPOUNDS WHICH MAY BE CHARACTERIZED AS PHOSPHONATES OF DIHYDROAROMATIC NITROGEN HETEROCYCLICS HAVE MANY USES INCLUDING THEIR USE AS BIOCIDES SUCH AS BACTERIOCIDES, HERBICIDES, CORROSION INHIBITORS, CHELATING AGENTS, ETC.

United sates Patent "once 3,830,815 Patented Aug. 20, 1 974 3,830,815 DIALKYL-LZ-DIHYDROQUINOLINE AND 1,2-

DIHYDROISOQUINOLINE PHOSPHONATES Derek Redmore, Ballwin, Mo., assignor to Petrolite Corporation, Wilmington, Del. No Drawing. Continuation of abandoned application Ser. No. 733,328, May 31, 1968. This application Mar. 27, 1 1973, Ser. No. 345,442

Int. Cl. C07d 33/12, 35/14 U.S. Cl. 260-283 P Claims ABSTRACT OF THE DISCLOSURE Nitrogen-heterocyclic phosphonates wherein the phosphonate group is orthoor parato the nitrogen heterocyclic group, where the compounds are characterized as follows:

0- (ortho substituted) and -N (para substituted) wherein the dotted line represents a cyclic structure which cyclic structure may be the sole cyclic structure, or may be' attached to other cyclic groups.

These nitrogen heterocyclic phosphonates are prepared by reacting an aromatic nitrogen heterocyclic compound, wherein the nitrogen atom is in the form of a salt or a quaternary, with a phosphite salt, preferably in the form of esters of the phosphite as exemplified by the following equation:

These compounds which may be characterized as phosphonates of dihydroaromatic nitrogen heterocyclics have many uses including their use as biocides such as bacteriocides, herbicides, corrosion inhibitors, chelating agents, etc.

This application is a continuation of pending Application Ser. No. 733,328, filed on May 31, 1968, now abandoned, and the following applications are divisional applications of Application Ser. No. 733,328: copending Application Ser. No. 107,052, filed on I an. 18, 1 971; copending Application Ser. No. 107,558, filed on Jan. 18, 1971; copending Application Ser. No. 117,082, filed on Feb. 19, 1971, now US. Pat. No. 3,770,750. Application Ser. No.

107,557, filed on Jan. 18, 1971, was a divisional application of parent Application Ser. No. 733,328 and was copending therewith and became U.S. Pat. No. 3,694,144 on Sept. 26, 1972.

This invention relates tonitrogen-heterocyclic phosphonates. More particularly this invention relates to nitrogen-heterocyclic phosphonates wherein the phosphonate group is ortho or para to the heterocyclic nitrogen group. Still more particularly, this invention relates to compounds characterized by the following groupszz (para substituted) This invention also relates to uses for these compounds for example as biocides such as bacteriocides, herbicides, corrosion inhibitors, chelating agents, etc.

Any nitrogen heterocyclic having an available ortho and/or para position capable of being activated by salt or quaternary formation of the nitrogengroupv so. as to promote reaction with salts of' phosphite esters: can be employed. This includes heterocyclics having one or more rings, where at least one ring has a nitrogen heterocyclic group and the other rings are carbocyclic or heterocyclic, i.e.,' they may contain oxygen or other non-carbon elements in the ring, etc. This may be illustrated by the following equations:

R, "R4, I 7,

| R5 11, MP(OR1): Bi

Ra Ra R 7 E k i I N R:

substituted group, for example, alkyl, cycloalkyl, aryl, alkaryl,

aralkyl, etc. R is an ester moiety for example alkyl, aryl, cycloalkyl, aralkyl, alkaryl, etc. oxyalkylated groups, etc.

The groups of R to R may also be further substituted provided the substituted groups do not interfere with the reaction.

Any of the R to R groups may also be joined to an adjacent group so as to form a ring provided ortho and/or para positions are available for substitution, for example in the following aromatic type ring systems:

Representative?examples of heterocyclicreactants include pyr-idinesand'benzoand 'dibenzo-' derivatives" of -pyridine,'for example, pyridine,alkylated pyridines' such as Z-picoline;3=picoline, 4-picoline,'etc;, 2,4=luti'dine,;'2,6-

.lutidine; 2-,'3=lutidine, -etc., 'collidines, etc.-q'uinoline and alkylated quinolines etc. isoquinolinea and alkylated isoquinolines, etc. phenanthridines, and substituted phenanthridines, etci acridines' and 'substitutedacridines, etc.

The nitrogen group in the heterocyclic ring is reacted with an acid or a quaternizing agent to activate the ring. The phosphorus contain ing reactant is, a metal salt of phosphorus acid; preferablyin the-form ofgan alkali metal salt in which .the metalis directly bondedto phosphorus In order to prevent" undesirable side reactions the phosphorus acid is used in the form of a derivative preferably as a diester.

.7 Where the phosphite ester containsmore thanonephosphite unit, a plurality of heterocyclic units may be joined thereto, for example O O ll II In general, the reaction is carried out in annincrt solvent which is water free at a temperature and time sufficient to promote the desired reaction. Ether solvents such as diethyl ether, dioxane andtetrahydrofuran are useful as well as aromatic hydrocarbon solvent like benzene, toluene, etc. Particularly useful are dipolar aprotic solvents such as dimethyl sulfoxide, dimethyl formamide N-methyl pyrrolidone. Combinations of these various types of solvents can also be advantageously used. Temperature and time are interrelated. Thus, a temperature of from 30 to the decomposition temperature of reactants and products can be employed, the upper limit of temperature being generally about 150 C., for a time of from 05-10 hours but preferably 1-3 hours. The inorganic salt is separated from the organic layer by filtration or by water extraction and the phosphonate derivative is separated from the organic layer. In addition the reaction is best carried out on an inert atmosphere such as nitrogen, argon, etc. In this way the attack of oxygen on phosphite salts and on the products is prevented. i

The following examples are presented by way-of illustration and not of limitation. r I

Example 1 I l I Preparation of diethyl 10-methyl-9,10- dihydroacridine-9-phosphonate V Acridine-. (5( g.) was reacted with dimethyl (35.2 g.) in benzene to form N-methyl acridinium methois added to a stirred suspension of the acridinium quaternary during 15 minutes.- A mildly exothermicreaction occurred. After heating at C. for two hours the mix- Example 2 Preparation of diethyl 9,10-dihydro acridine-9- phosphonate To acridine hydrobromide (26 g.) suspended in toluene (100 ml.) was added a solution of the sodio derivative of diethyl phosphite in dioxane (50 ml.) (prepared from diethyl phosphite (13.8 g.) and sodium (2.3 g.)) in 20 minutes. The reactants were heated under reflux for two hours and allowed to cool to roomtemperature. After the addition of water (100 ml.) the organic layer was separated and the aqueous layer extracted with chloroform. Evaporation of the combined organic extracts produced 20 g. (65%) of crude product. Recrystallization from benzene/hexane gave the pure acridine phosphonate mp 189- 90. The product showed infrared absorption at 3.1;; (N-H), and 8.3 (P=O). Analysis: N=4.5l%; P=9.79%. Calculated for C H NO P: N=4.42%; Pl=9.78%.

The structure of the product is Example 3 Preparation of diethyl 10-methyl-9,l0-dihydro acridine-9- phosphonate --Acridine was converted to the quaternary N-methyl acridinium iodide by reaction with methyl iodide. This quaternary was reacted with thesodio derivative of direthyl phosphitg dioxane following the procedure of Example 1. The product obtained using the i solation 'pr'olcedure of Example 1 was identical with that product in all respects. Yield-55 Example 4 Preparation of diisopropyl 10-methyl-9,10-dihydro acridine-9-phosphonate N-methyl acridinium methosulfate (from acridine (17.9 g.) and dimethyl sulfate (12.6 g.) suspended in toluene (75 ml.) was treated with the sodio derivative or diisopropyl phosphite in dioxane (50 ml.) (prepared from diisopropyl phosphite (16.6 g.) and sodium (2.3 g.)). The reaction was brought to completion by heating at 90 for six hours. Additionof water and isolation as in Example 1 gave the acridinephosphonate (40% yield) mp 124-5" after crystallization from benzene-hexane. The product had the structure;

Analysis Found: N=3.85%; P=8.39%. Calculated for C H NO P: Nl=3.90%; P=8.64%.

Example 5 Preparation of diethyl 2-methyl 1,2-dihydro isoquinolinel-phosphonate N-methyl isoquinolinium iodide (94.5 g.) was suspended in benzene (200 ml.) by vigorus stirring while the sodio derivative of diethyl phosphite in dioxane (100 ml.) (from diethyl phosphite (49 g.) and sodium (8.2 g.)) was added dropwise in 20 minutes. The reaction was carried out under an argon atmosphere. After the addition the mixture was heated for one hour at -80 and allowed to cool to room temperature before the addition of water (200 ml.). The aqueous layer was separated and extracted with benzene (2 times with ml.). Evaporation of the combined organic fractions gave the product as a dark oil 71 g. (72%).

Infrared absorption at 8.05,u. (P=O), 9.8 (P-O-C) are consistent with structure.

Nuclear Magnetic Resonance (NMR) absorption at 8.87 and 6.051 (OC H5), 7.O21-"(NCH 5231- (H at C and 4.81- and 3.971- (H at C and C The product contains R: 10.45%. Calculated 11.0%.

The following is the structure of the product.

N-CH! P=0 ((k C Example 6 Preparation of diethyl 1,2-dihydroisoquinoline l-phosphonate Isoquinoline hydrobromide (19 g.) was suspended in benzene ml.) by vigorous stirring while the sodio derivative of diethyl phosphite in dioxane (50 ml.) (from diethyl phosphite 13.8 g.) and sodium (2.3 g.)) was added during ten minutes. The reaction was completed by heatin'g'under reflux for one hour. The product was isolated as a dark oil following the procedure of Example 5 in 75% yield. The infrared spectrum showed characteristic absorption at 8.0 (P=O). The product is the dihydroisoquinoline phosphonate of the following formula:

( CaHz):

3,830,815 p ht jjriate in"80 yield'f'lhe dih'ydro-'phnanthridirl'e"phos pfiafiate had the"followingstructure' i Preparation of diethyl l-propyl 1,2-dihydroquino me 2- phosphonate and diethyl l-propyl 1,4-dihydroquinoline 4-phosphonate N-propyl quinolinium iodide (66.5- g.) was suspended in benzene by vigorous stirring while the sodio derivative of diethyl phosphite (from diethyl phosphite (30.5 g.)

and sodium (5.15 g.)) in dio'xane (100 ml.) was added during twenty minutes. The reaction was completed by heating at 80 forqjtwo hour-'sgAfter cooling, water (200 ml.) was added and the product isolated as a dark yellow oil as in Example 5: Yield 52 g. (76%). Infrared absorption at 8.0;. (P=O) and 9.8; (P-O-C) are in agreement with a dihydroquinoline phosphonate structure.

phosphonate and diethyl-,l-methyl 1,4-dihydropyridine 4-phosphonate p l t To a stirred suspension of. N-r n ethyl pyridinium methosulfate (205 g.) in toluene (250 ml.) under an 5 argon atmosphere was added sodio' diethyl phosphite The product also contains small amounts of the 4- (from difithyl P I g and "Sodium isomer: in dioxane (200 ml.)during 20 minutes; The rea'ction was brought to completion by heating at 95 for- 3 hours. To the crude product was added"ethe'r (200 m1.) #and 3 solid (inorganic) was filtered 'otf. "Evaporation of the solvent under reduced pressure gave the product -'as="a dark brown oil which was readily "soluble in water "and in aromatic hydrocarbons/The product is a mixture-repl resented by the formulae:

A Y "Example 9 Q J? I 1 Preparation of diethyl l-methyl 1,2-dihydropyridine 2- P(OC2H5)2 H II II P (O C2H5) 2 Example 8 l i 4 Preparation of diethyl S-methyl 5,6-dihydrophenanthridine fi-phosphonate N N H N-methyl phenanthridin-ium iodide g.) was sus- Ii/Ie pended in toluene (150 m1.) and reacted with sodio di- 45 4 ethyl phosphite (22.5 g.) in diox'ane (100 ml.) under a nitrogen blanket. After heating for two hours at Srnce the above Examplesfillustrate the general meththe reaction mixture was cooled and water (200 ods of preparation, additional. examples are presented in ml.) was added. Benzene extraction gave the crude phosthe following Table 3 I TABI ll ljI i Reaetants it:

Quaternary a 1 1x.-- "Heterocyclic' .or salt-w P 9 Phite 1 X Product... apiconnesna- Mthi0dide--. Nafirocznm l.

i ,-J "1'= oni. ."i 1 v N C Plus Product Plus . 0 (lime...

N H a...

As is quite evident, other nitrogen heterocyclics and phosphites are useful in my invention. It is, therefore, not only impossible to attempt a comprehensive catalogue of such compounds, but to attempt to describe the invention in its broader aspects in terms of specific heterocyclics and phosphites reacted would be too voluminous and unnecessary since one skilled in the art could by following the description of the invention herein select a useful reactant. This invention lies in the reaction of suitable heterocyclics and phosphites and their individual compositions are important only in the sense that they react to form useful products. To precisely define each specific useful heterocyclic in light of the present disclosure would merely call for chemical knowledge within the skill of the art in a manner analogous to a mechanical engineer who prescribes in the construction of a machine the proper materials and the proper dimensions thereof. From the description in this specification and v with the knowledge of a chemist, one will know or deduce with confidence the applicability of specific hetero- CORROSION TESTS The test procedure includes measurement of the corrosive action of the fluids inhibited by the compositions herein described upon sand-blasted SAE-1020 steel coupons under conditions approximating those found in an actual producing well, and the comparison thereof with results obtained by subjecting identical test coupons to the corrosive action of the identical fluids containing no inhibitor.

In the present tests clean pint bottles are charged with 440 m1. of a synthetic brine, which contains 42 g. of sodium chloride, 14 g. calcium chloride, 1 g. of sodium sulfate and 17 g. of magnesium chloride per liter, saturated with hydrogeng-sulfide and a predetermined amount of inhibitor is then added. The inhibitor concentration is based on the total volume of fluid. Bottle caps holding three coupons are then placed tightly on the bottles. The bottles are then placed on a wheel contained in an oven and rotated for 4 hours at 95 F. Corrosion rates are then measured using the three coupons in each bottle as electrodes in conjunction with an instrument for measurement of instantaneous corrosion rates. Percent protection is calculated from where R is corrosion rate of uninhibited fluids R is corrosion rate of inhibited fluids 3,830,815 1 1 The compositions of this invention give good corrosion pgopyl lg -glihydgoqhixfoline g iihosphonate and diethyl}; protection in the above test as shown by the data in the propyl 1,4-dihydroquinoline;-.4;ph95phonate. following table. 2. The compoundof-elai n -diethyl-'-2-methyl 1,2-dihydroisoquinolinesl-phos Coneenq 3. The compound. mf', Pmtecmn' hydroisoquinoline l-phosphonate.

Compound p.p.m. percent v I v 4. The compound ofclaun 1 whlch is diethyl l-propyl gfff: 50 89 1,2-dihydroquinoline 2-phosphonate.

100 94 5. The compound of claim 1 which is diethyl l-propyl 7m: 50 88 10 lA-dihydroquinoline 4-phosphonate.

92 3 References Cited Commerclal. 50 76 I I Inhibit" 84 FOREIGN PATENTS Having thus described my invention what I claim as 15 9 2/1966 Poland P new and desire to obtain by Letters Patent is:

1. A compound selected from the group consisting of DONALD DAUS' Primary Examiner diethyl 2-methyl 1,2-dihyd1'oisoquinoline 1-phosphonate, M. C. VAUGHN, Assistant Examiner diethyl 1,2-dihydroisoquinoline l-phosphonate, diethyl 1-' 

